KHSRP knockdown inhibits papillary renal cell carcinoma progression and sensitizes to gemcitabine.

Patients diagnosed with papillary renal cell carcinoma (pRCC) exhibit a high rate of clinical metastasis; however, the underlying molecular mechanism is unclear. In this study, KH-type splicing regulatory protein (KHSRP) participated in pRCC progression and was associated with metastasis. It was positively correlated with the hallmark of epithelial-mesenchymal transition. KHSRP inhibition effectively alleviated the cellular function of migration and invasion. Additionally, KHSRP knockdown inhibited the proliferative ability of pRCC cells. A pharmaceutical screening was based on the KHSRP protein structure. Gemcitabine (Gem) decreased KHSRP expression. UIO-66@Gem@si-KHSRP (UGS) nanoparticles (NPs) were prepared for targeted delivery and applied in both in vitro and in vivo experiments to explore the clinical transition of KHSRP. UGS NPs exhibited better performance in inhibiting cellular proliferation, migration, and invasion than Gem. Additionally, the in vivo experiment results confirmed their therapeutic effects in inhibiting tumor metastasis with excellent biosafety. The silico analysis indicated that KHSRP knockdown increased cytotoxic cell infiltration in the tumor microenvironment to potentiate anti-tumor effects. Thus, KHSRP can promote pRCC progression as an oncogene and serve as a target in clinical transition through UGS NP-based therapy.

Comparison of grain traits and genetic diversity between Chinese and Uruguayan soybeans (Glycine max L.).

Soybeans (Glycine max L.), originating in China, were introduced to South America in the late 19th century after passing through North America. South America is now a major soybean-producing region, accounting for approximately 40% of the global soybean production. Crops like soybeans gradually adapt to the local climate and human-selected conditions, resulting in beneficial variations during cultivation in different regions. Comparing the phenotypic and genetic variations in soybeans across different regions is crucial to determining the variations that may enhance soybean productivity. This study identified seed-related traits and conducted a genetic diversity analysis using 46 breeding soybean varieties from China and Uruguay. Compared to the Chinese soybean germplasm, the Uruguayan equivalent had a lower 100-grain weight, higher oil content, lower protein content, and higher soluble sugar content. Using ZDX1 gene chips, genetic typing was performed on the 46 breeding varieties. Cluster analysis based on SNP sites revealed significant differences in the genetic basis of Sino-Uruguayan soybean germplasm. Selection analysis, including nucleotide polymorphism (π) and fixation indexes (Fst), identified several genomic regions under selection between Sino-Uruguayan soybean germplasm. The selected intervals significantly enriched gene ontology (GO) terms related to protein metabolism. Additionally, differentiation occurred in genes associated with the oil content, seed weight, and cyst nematodes between Sino-Uruguayan soybean germplasm, such as GmbZIP123 and GmSSS1. These findings highlight the differences in seed-related phenotypes between Sino-Uruguay soybean germplasm and provide genomic-level insights into the mechanisms behind phenotypic differences, offering valuable references for understanding soybean evolution and molecular breeding.

Overexpression of the Purple Perilla (Perilla frutescens (L.)) FAD3a Gene Enhances Salt Tolerance in Soybean.

The increasingly serious trend of soil salinization inhibits the normal growth and development of soybeans, leading to reduced yields and a serious threat to global crop production. Microsomal ω-3 fatty acid desaturase encoded by the FAD3 gene is a plant enzyme that plays a significant role in α-linolenic acid synthesis via regulating the membrane fluidity to better accommodate various abiotic stresses. In this study, PfFAD3a was isolated from perilla and overexpressed in soybeans driven by CaMV P35S, and the salt tolerance of transgenic plants was then evaluated. The results showed that overexpression of PfFAD3a increased the expression of PfFAD3a in both the leaves and seeds of transgenic soybean plants, and α-linolenic acid content also significantly increased; hence, it was shown to significantly enhance the salt tolerance of transgenic plants. Physiological and biochemical analysis showed that overexpression of PfFAD3a increased the relative chlorophyll content and PSII maximum photochemical efficiency of transgenic soybean plants under salt stress; meanwhile, a decreased accumulation of MDA, H2O2, and O2•-, increased the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbic acid peroxidase (APX), as well as the production of proline and soluble sugar. In summary, the overexpression of PfFAD3a may enhance the salt tolerance in transgenic soybean plants through enhanced membrane fluidity and through the antioxidant capacity induced by C18:3.

Time series canopy phenotyping enables the identification of genetic variants controlling dynamic phenotypes in soybean.

Advances in plant phenotyping technologies are dramatically reducing the marginal costs of collecting multiple phenotypic measurements across several time points. Yet, most current approaches and best statistical practices implemented to link genetic and phenotypic variation in plants have been developed in an era of single-time-point data. Here, we used time-series phenotypic data collected with an unmanned aircraft system for a large panel of soybean (Glycine max (L.) Merr.) varieties to identify previously uncharacterized loci. Specifically, we focused on the dissection of canopy coverage (CC) variation from this rich data set. We also inferred the speed of canopy closure, an additional dimension of CC, from the time-series data, as it may represent an important trait for weed control. Genome-wide association studies (GWASs) identified 35 loci exhibiting dynamic associations with CC across developmental stages. The time-series data enabled the identification of 10 known flowering time and plant height quantitative trait loci (QTLs) detected in previous studies of adult plants and the identification of novel QTLs influencing CC. These novel QTLs were disproportionately likely to act earlier in development, which may explain why they were missed in previous single-time-point studies. Moreover, this time-series data set contributed to the high accuracy of the GWASs, which we evaluated by permutation tests, as evidenced by the repeated identification of loci across multiple time points. Two novel loci showed evidence of adaptive selection during domestication, with different genotypes/haplotypes favored in different geographic regions. In summary, the time-series data, with soybean CC as an example, improved the accuracy and statistical power to dissect the genetic basis of traits and offered a promising opportunity for crop breeding with quantitative growth curves.

Genome-wide signatures of the geographic expansion and breeding of soybean.

Soybean is a leguminous crop that provides oil and protein. Exploring the genomic signatures of soybean evolution is crucial for breeding varieties with improved adaptability to environmental extremes. We analyzed the genome sequences of 2,214 soybeans and proposed a soybean evolutionary route, i.e., the expansion of annual wild soybean (Glycine soja Sieb. & Zucc.) from southern China and its domestication in central China, followed by the expansion and local breeding selection of its landraces (G. max (L.) Merr.). We observed that the genetic introgression in soybean landraces was mostly derived from sympatric rather than allopatric wild populations during the geographic expansion. Soybean expansion and breeding were accompanied by the positive selection of flowering time genes, including GmSPA3c. Our study sheds light on the evolutionary history of soybean and provides valuable genetic resources for its future breeding.

Identification of prognostic factors for predicting survival of patients with malignant adrenal tumors: A population-based study.

Background: This study aimed to identify the prognostic factors for overall survival (OS) and cancer-specific survival (CSS) in patients with malignant adrenal tumors and establish a predictive nomogram for patient survival. Methods: The clinical characteristics of patients diagnosed with malignant adrenal tumors between 1988 and 2015 were retrieved from the Surveillance, Epidemiology and End Results (SEER) database. As the external validation set, we included 110 real-world patients from our medical centers. Univariate and multivariate Cox regressions were implemented to determine the prognostic factors of patients. The results from Cox regression were applied to establish the nomogram. Results: A total of 2,206 eligible patients were included in our study. Patients were randomly assigned to the training set (1,544; 70%) and the validation set (662; 30%). It was determined that gender, age, marital status, histological type, tumor size, SEER stage, surgery, and chemotherapy were prognostic factors that affected patient survival. The OS prediction nomogram contained all the risk factors, while gender was excluded in the CSS prediction nomogram. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) indicated that the nomogram had a better predictive performance than SEER stage. Moreover, the clinical impact curve (CIC) showed that the nomograms functioned as effective predictive models in clinical application. The C-index of nomogram for OS and CSS prediction was 0.773 (95% confidence interval [CI]: 0.761-0.785) and 0.689 (95% CI: 0.675-0.703) in the training set. The calibration curves exhibited significant agreement between the nomogram and actual observation. Additionally, the results from the external validation set also presented that established nomograms functioned well in predicting the survival of patients with malignant adrenal tumors. Conclusions: The following clinical variables were identified as prognostic factors: age, marital status, histological type, tumor size, SEER stage, surgery, and chemotherapy. The nomogram for patients with malignant adrenal tumors contained the accurate predictive performance of OS and CSS, contributing to optimizing individualized clinical treatments.

A nomogram incorporating red blood cell indices to predict post-stroke cognitive impairment in the intracerebral hemorrhage population.

Background: Post-stroke cognitive impairment (PSCI) plagues 20-80% of stroke survivors worldwide. There is a lack of an easy and effective scoring tool to predict the risk of PSCI in intracerebral hemorrhage (ICH) patients. We aimed to develop a risk prediction model incorporating red blood cell (RBC) indices to identify ICH populations at risk of PSCI. Methods: Patients diagnosed with ICH at the stroke center were consecutively enrolled in the study as part of the development cohort from July 2017 to December 2018, and of the validation cohort from July 2019 to February 2020. Univariable and multivariable analyses were applied in the development cohort to screen the patients for PSCI risk factors. Then, a nomogram based on RBC indices and other risk factors was developed and validated to evaluate its performance in predicting PSCI occurrence. Results: A total of 123 patients were enrolled in the development cohort, of which 69 (56.1%) were identified as PSCI, while 38 (63.3%) of 60 patients in the validation cohort were identified as PSCI. According to the multivariate analysis, seven independent risk factors, including three RBC indices (hemoglobin, mean corpuscular volume, RBC distribution width), as well as age, education level, hematoma volume, and dominant-hemisphere hemorrhage were incorporated into the model. The nomogram incorporating RBC indices displayed good discrimination and calibration. The area under the receiver operating characteristic curve was 0.940 for the development cohort and 0.914 for the validation cohort. Decision curve analysis and clinical impact curve showed that the nomogram was clinically useful. Conclusion: RBC indices are independent and important predictors of PSCI. A nomogram incorporating RBC indices can be used as a reasonable and reliable graphic tool to help clinicians identify high cognition impairment-risk patients and adjust individualized therapy.

An enhancing effect attributed to a nonsynonymous mutation in SOYBEAN SEED SIZE 1, a SPINDLY-like gene, is exploited in soybean domestication and improvement.

Soybean (Glycine max) was domesticated from its wild relative Glycine soja. One-hundred-seed weight is one of the most important domesticated traits determining soybean yield; however, its underlying genetic basis remains elusive. We characterized a soybean seed size 1 (sss1) mutant featuring large seeds compared to its wild-type background. Positional cloning revealed that the candidate gene GmSSS1 encoded a SPINDLY homolog and was co-located in a well-identified quantitative trait locus (QTL)-rich region on chromosome 19. Knocking out GmSSS1 resulted in small seeds, while overexpressing GmSSS1/Gmsss1 induced large seeds. Modulating GmSSS1/Gmsss1 in transgenic plants can positively influence cell expansion and cell division. Relative to GmSSS1, one mutation leading to an E to Q substitution at the 182nd residue in Gmsss1 conferred an enhancing effect on seed weight. GmSSS1 underwent diversification in wild-type and cultivated soybean, and the alleles encoding the Gmsss1-type substitution of 182nd -Q, which originated along the central and downstream parts of the Yellow River, were selected and expanded during soybean domestication and improvement. We cloned the causative gene for the sss1 mutant, which is linked with a seed weight QTL, identified an elite allele of this gene for increasing seed weight, and provided new insights into soybean domestication and breeding.

Transplantation of fecal microbiota from APP/PS1 mice and Alzheimer's disease patients enhanced endoplasmic reticulum stress in the cerebral cortex of wild-type mice.

Background and purpose: The gut-brain axis is bidirectional and the imbalance of the gut microbiota usually coexists with brain diseases, including Alzheimer's disease (AD). Accumulating evidence indicates that endoplasmic reticulum (ER) stress is a core lesion in AD and persistent ER stress promotes AD pathology and impairs cognition. However, whether the imbalance of the gut microbiota is involved in triggering the ER stress in the brain remains unknown. Materials and methods: In the present study, fecal microbiota transplantation (FMT) was performed with gut microbiota from AD patients and APP/PS1 mice, respectively, resulting in two mouse models with dysregulated gut microbiota. The ER stress marker protein levels in the cerebral cortex were assessed using western blotting. The composition of the gut microbiota was assessed using 16S rRNA sequencing. Results: Excessive ER stress was induced in the cerebral cortex of mice after FMT. Elevated ER stress marker proteins (p-perk/perk, p-eIF2α/eIF2α) were observed, which were rescued by 3,3-dimethyl-1-butanol (DMB). Notably, DMB is a compound that significantly attenuates serum trimethylamine-N-oxide (TMAO), a metabolite of the gut microbiota widely reported to affect cognition. Conclusion: The findings indicate that imbalance of the gut microbiota induces ER stress in the cerebral cortex, which may be mediated by TMAO.

[Comparative analysis of powder and piece decocting processes of Yinqiao Powder based on determination of multiple primary components].

The present study established specific chromatograms and a method for determining multiple primary components in Yinqiao Powder decoctions and compared the change rules of chemical composition in powder and piece decocting processes of Yinqiao Powder to provide a scientific basis for the modern research of preparations of Yinqiao Powder. Powder and piece decoctions of Yinqiao Powder were prepared. The specific chromatograms were determined and the content of 17 primary components was measured by high-performance liquid chromatography(HPLC), including adoxosidic acid, neochlorogenic acid, forsythoside E, loganic acid, chlorogenic acid, cryptochlorogenic acid, sweroside, forsythoside Ⅰ, forsythoside H, forsythoside A, isochlorogenic acid B, E-aldosecologanin, hesperidin, phillyrin, arctiin, liquiritigenin, and dipotassium glycyrrhizinate. The effect of decocting time on the chemical composition in powder and piece decoctions of Yinqiao Powder was investigated. As a result, the specific chromatogram similarities of powder decoctions of Yinqiao Powder with different decocting time were high, which indicated that their chemical compositions were similar, while the similarities of piece decoctions were low, suggesting similar chemical compositions with big differences. In powder decoctions, the concentrations of neochlorogenic acid, cryptochlorogenic acid, forsytherin H, and isochlorogenic acid B increased with the prolongation of decocting time, and those of adoxosidic acid, forsythoside E, forsythoside Ⅰ, E-aldosecologanin, phillyrin, dipotassium glycyrrhizinate, loganic acid, arctiin, sweroside, and liquiritigenin increased firstly and tended to be stable, while those of forsythoside A, chlorogenic acid, and hesperidin increased firstly and then decreased. In piece decoctions, the concentration of chlorogenic acid increased firstly and then decreased with the prolongation of decocting time, while those of the remaining 16 components showed an upward trend. The concentrations of adoxosidic acid, forsythoside E, forsythoside Ⅰ, E-aldosecologanin, phillyrin, dipotassium glycyrrhizinate, forsythoside A, forsythoside H, and chlorogenic acid in powder decoctions were higher than those in piece decoctions. The concentrations of hesperidin, loganic acid, phillyrin, sweroside, liquiritigenin, neochlorogenic acid, and cryptochlorogenic acid in powder decoctions were higher than those in piece decoctions within 40 min of decocting. The concentration of isochlorogenic acid B in powder decoctions was lower than that in piece decoction 10 min after decocting. The results showed that the decocting time and particle size of raw medicinal materials had certain effects on the content of chemical components in decoctions of Yinqiao Powder. Compared with the piece decocting, the powder decocting could achieve faster resolution of chemical components and higher concentrations, which confirmed the scientific evidence of the traditional powder decocting method of Yinqiao Powder. For the piece decocting of prescriptions of Yinqiao Powder, extraction time should be prolonged and extraction times should be increased to achieve the same effect as the powder decocting.

Noncoding-RNA mediated high expression of zinc finger protein 268 suppresses clear cell renal cell carcinoma progression by promoting apoptosis and regulating immune cell infiltration.

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant kidney tumors with a poor prognosis. Accumulating evidence proves that zinc finger protein 268 (ZNF268) is associated with tumor progression, but the detailed regulatory functions of ZNF268 in ccRCC require further exploration. Thus, here we aim to characterize the role of ZNF268 in ccRCC. The clinical significance of ZNF268 was evaluated using The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Subsequently, tumor-infiltrating immune cells, as well as upstream noncoding RNAs (ncRNAs) related to the tumor-suppressing function of ZNF268, were identified by in silico analyses. The expression of ZNF268 was significantly decreased in ccRCC samples compared with adjacent normal tissues. In addition, ZNF268 expression was negatively correlated with tumor progression and positively correlated with overall and disease-specific survival. TCGA and GTEx databases proved the potential tumor-suppressing function, which was measured both in vitro and in vivo after ZNF268 over-expression. Overexpression of ZNF268 effectively inhibited the proliferation, migration, invasion and promotied apoptosis of the Caki-1. The level of ZNF268 was positively related to the immune cell infiltration in the tumor. Moreover, we determined that the AC093157.1/miR-27a-3p axis can potentially regulate ZNF268 function in ccRCC. Our work describes a novel ncRNA-mediated ZNF268 function in ccRCC. ZNF268 acts as a tumor suppressor, and it is associated with apoptosis and immune cell infiltration in ccRCC.

Rapid identification of chemical constituents in Yinqiao powder using ultra-high-performance liquid chromatography coupled to quadrupole-time-of-flight tandem mass spectrometry using data filtering strategy.

Yinqiao powder is a classic and effective prescription for the treatment of many kinds of pneumonia in China. To date, its chemical constituents have not been determined. A comprehensive identification of its chemical constituents provided a structural basis to discover the potential anti-pneumonia ingredients in Yinqiao powder. This paper developed an ultra-high-performance liquid chromatography (UHPLC) coupled to quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS) analysis with diagnostic product ions and neutral loss filtering strategy and applied it for the comprehensive chemical profiling of Yinqiao powder, which simplified the structural elucidation of chemical constituents in Yinqiao powder. A total of 124 compounds, comprising 8 C6-C2 glucoside conjugates, 28 iridoid glycosides, 14 lignans, 21 phenylethanol glycosides, 20 triterpenoid saponins, 9 chlorogenic acids, and 24 flavonoids, were rapidly identified in Yinqiao powder, and 32 of these were characterized by comparing their MS/MS data and retention time with reference standards. The results indicated that UHPLC-QTOF-MS/MS method coupled with data filtering strategy was feasible and rational to identify the complex chemical constituents of Yinqiao powder, which would be conducive to discover the active ingredients of Yinqiao powder for the treatment of pneumonia and establish its quality standard.

Comprehensive chemical profiling of the flowers of Citrus aurantium L. var. amara Engl. and uncovering the active ingredients of lipid lowering.

The flowers of Citrus aurantium L. var. amara Engl. (FCAVA) is popularly consumed as an edible tea for anti-hyperlipidemia. But the active ingredients are not fully clear. In this study, ultra-high performance liquid chromatography coupled to quadrupole time of flight tandem mass spectrometry (UHPLC-QTOF-MS/MS) with diagnostic product ions and neutral loss filtering strategy were successfully used for comprehensive characterization of chemical components in FCAVA. A total of 228 constituents, including 46 organic acids, 12 coumarins and 170 flavonoids, were tentatively characterized (30 confirmed with reference standards). Among them, nineteen flavonoids in 70 batches of FCAVA from different geographical origins were quantified by UHPLC tandem triple quadrupole mass spectrometry (QQQ-MS), which displayed satisfactory linearity, sensitivity, precision, accuracy, and stability. According to analytical results, the distribution of nineteen flavonoids in different geographical origins of FCAVA was clarified. In addition, the effect on LDL uptake of twenty-five flavonoids was investigated in HepG2 cell. It was found that the acacetin, diosmetin and rutin dose-dependently enhanced LDL uptake in HepG2 cells comparing to control. Furthermore, in a hyperlipidemia C57BL/6J mice model, administration of acacetin, diosmetin and rutin (30 mg/kg/d, intragastric, for three weeks) significantly decreased the levels of total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) in plasma, respectively. Overall, these findings indicated the potential of FCAVA in the development of functional food or medicine for the prevention and treatment of hyperlipidemia, which could be considered for the improvement of quality standardization of FCAVA.

Dissection of the practical soybean breeding pipeline by developing ZDX1, a high-throughput functional array.

KEY MESSAGE: We developed the ZDX1 high-throughput functional soybean array for high accuracy evaluation and selection of both parents and progeny, which can greatly accelerate soybean breeding. Microarray technology facilitates rapid, accurate, and economical genotyping. Here, using resequencing data from 2214 representative soybean accessions, we developed the high-throughput functional array ZDX1, containing 158,959 SNPs, covering 90.92% of soybean genes and sites related to important traits. By application of the array, a total of 817 accessions were genotyped, including three subpopulations of candidate parental lines, parental lines and their progeny from practical breeding. The fixed SNPs were identified in progeny, indicating artificial selection during the breeding process. By identifying functional sites of target traits, novel soybean cyst nematode-resistant progeny and maturity-related novel sources were identified by allele combinations, demonstrating that functional sites provide an efficient method for the rapid screening of desirable traits or gene sources. Notably, we found that the breeding index (BI) was a good indicator for progeny selection. Superior progeny were derived from the combination of distantly related parents, with at least one parent having a higher BI. Furthermore, new combinations based on good performance were proposed for further breeding after excluding redundant and closely related parents. Genomic best linear unbiased prediction (GBLUP) analysis was the best analysis method and achieved the highest accuracy in predicting four traits when comparing SNPs in genic regions rather than whole genomic or intergenic SNPs. The prediction accuracy was improved by 32.1% by using progeny to expand the training population. Collectively, a versatile assay demonstrated that the functional ZDX1 array provided efficient information for the design and optimization of a breeding pipeline for accelerated soybean breeding.

Profiling of naturally occurring folates in a diverse soybean germplasm by HPLC-MS/MS.

Soybean is a rich source of folates. We optimised the extraction and detection of folates from soybean seeds by HPLC-MS/MS and analysed the folate content and composition of 1074 accessions. Total folate content ranged from 64.51 to 691.24 µg/100 g fresh weight, with 10-fold variation, and 60 elite accessions with over 400 µg/100 g of total folate were identified. The most abundant component was 5-CHO-H4folate, which accounted for an average of 60% of total folate content. Seed-coat colour, seed weight, ecoregion, and accession type significantly affected soybean folate content. Furthermore, 5-CH3-H4folate correlated positively with seed protein (r = 0.24***) and negatively with oil (r = -0.26***). The geographical distribution of folate according to accession origin revealed that accessions from Northeast China contain higher amounts of total folate and 5-CHO-H4folate. This study provides comprehensive and novel insights into the folate profile of soybean, which will benefit soybean breeding for folate enhancement.

Nystagmus Parameters of Supine Roll Test Correlates With Prognosis After Repositioning Maneuver in Horizontal Semicircular Canal Benign Paroxysmal Positional Vertigo.

Background: Positional nystagmus induced by supine roll test is characteristic for diagnosing horizontal semicircular canal benign paroxysmal positional vertigo (HC-BPPV). In this study, we aimed to explore the value of nystagmus parameters in by supine roll test (SRT) as prognostic factors in HC-BPPV. Methods: We retrospectively analyzed the nystagmus parameters of 813 patients diagnosed with HC-BPPV by the SRT model in the SRM-IV system through video nystagmography. Then we used the computer-controlled canalith repositioning procedure (CCRP) mode for treatment. Based on the outcomes, patients were divided into either the cured group or the resistant group. The 1:1 propensity score matching (PSM) was applied to minimize potential selection bias. Then univariable and multivariable analyses were performed to identify the association of nystagmus parameters and the efficacy of CCRP. Results: Among the 813 patients, 99 (12.2%) were classified in the resistant group. The right side of HC-BPPV patients was twice the number of the left side patients (537 vs. 276). PSM is used to pair resistant patients to the cured patients, in which 99 pairs were successfully matched. Results of univariate and multivariate analyses showed that patients in the resistant group have longer latency in the affected side [odds ratio (OR) = 1.231 (1.110-1.366); P < 0.001] and slower slow phase velocity (SPV) in the healthy side [OR = 0.957 (0.917-0.999); P = 0.045]. Conclusion: Nystagmus parameters may represent the characteristics of canalith. HC-BPPV patients with a longer latency in the affected side and slower SPV on the healthy side during SRT have a higher risk of HC-BPPV persisting after a single CCRP.

Combination of Total Psoas Index and Albumin-Globulin Score for the Prognosis Prediction of Bladder Cancer Patients After Radical Cystectomy: A Population-Based Study.

BACKGROUND: Sarcopenia as the loss of skeletal muscle mass is related with poor postoperative survival. This work purposed to evaluate the prognostic prediction of the total psoas index (TPI), albumin-globulin score (AGS), and the combination of TPI and AGS (CTA) in bladder cancer (BCa) patients after radical cystectomy. METHODS: BCa patients that received radical cystectomy between 2012 and 2020 were retrieved from our medical center. The calculation of TPI was based on the plain computed tomography images. The predictive effects of TPI, AGS, and CTA grade on survival of BCa patients were analyzed and compared with the albumin-globulin ratio (AGR) through the receiver operating characteristic (ROC) curves. A nomogram was further established based on the Cox regression results from CTA grade and clinicopathological characteristics, which are verified by the decision curve analysis (DCA). RESULTS: A total of 112 eligible patients diagnosed as BCa were included in this study for retrospective analysis. The patients with lower TPI or higher AGS grade (1/2) contained poorer overall survival (OS) and disease-free survival (DFS). Divided by CTA grade, there were 35 (31.25%) patients in grade 1 associated with the best postoperative prognosis, which was accompanied with increased TPI and decreased AGS. The CTA grade could better predict postoperative outcomes compared with TPI, AGR, and AGS for the highest area under the curve (AUC; 0.674 of OS and 0.681 of DFS). The 3- and 5-year OS and DFS nomograms were conducted based on CTA grade and clinical variables, with a higher predictive performance than the TNM stage. CONCLUSION: This study revealed that the novel index CTA functioned as an effective prognostic predictor for postoperative OS and DFS of BCa patients after radical cystectomy. Preoperative assessment of CTA would contribute to optimizing clinical therapies.

Effects of Hemodialysis on Prognosis in Individuals with Comorbid ERSD and ICH: A Retrospective Single-Center Study.

OBJECTIVES: End-stage renal disease (ESRD) is one of the most critical risk factors of intracerebral hemorrhage (ICH). We aimed to investigate the effects of maintenance hemodialysis on hematoma volume, edema volume, and prognosis in patients with comorbid ESRD and ICH. MATERIALS AND METHODS: Patients with comorbid ESRD and ICH were divided into two groups based on whether receiving maintenance hemodialysis. Hematoma and perihemorrhagic edema (PHE) volumes and relative edema ratio after admission were assessed on head computed tomography scans. RESULTS: During the initial diagnosis, the dialysis group had lower PHE volume (16.41 vs 35.90 mL, P = 0.010), total volume of hematoma and edema (31.58 vs 54.58 mL, P = 0.013), and relative edema ratio (0.57 vs 0.92, P = 0.033) than the non-dialysis group. In addition, the peak PHE volume (36.68 vs 84.30 mL, P < 0.001), peak total volume of hematoma and edema (53.45 vs 127.69 mL, P = 0.011), and peak relative edema ratio (1.12 vs 1.92, P = 0.001) within one week after onset were lower in the dialysis group than in the non-dialysis group. The dialysis group had a higher in-hospital mortality rate than the non-dialysis group (40% vs 10%, P = 0.007). At 1-year follow-up, the two groups had similar 1-year-mortality rates and modified Rankin Scale. CONCLUSIONS: Hemodialysis can prevent the enlargement of edema and reduce PHE volume shortly after onset. Although dialyzed patients had a higher in-hospital mortality rate, hemodialysis did not affect 1-year survival rate and functional neurologic scales.

Trajectory Analysis of Orthostatic Hypotension in Parkinson's Disease: Results From Parkinson's Progression Markers Initiative Cohort.

Background: Orthostatic hypotension (OH) in Parkinson's disease (PD) can lead to falls, impair quality of life, and increase mortality. A trajectory analysis of OH could be useful to predict and prevent the hypotension incidence early. Methods: The longitudinal data of 660 patients with PD with disease duration up to 12 years were extracted from an integrated PD database. We used latent class mixed modeling (LCMM) to identify patient subgroups, demonstrating trajectories of changes in orthostatic blood pressure (BP) over time. The optimal number of subgroups was selected by several criteria including the Bayesian Information Criterion. Baseline information comparison between groups and backward stepwise logistic regression were conducted to define the distinguishing characteristics of these subgroups and to investigate the predictors for BP trajectory. Results: We identified three trajectories for each orthostatic change of systolic blood pressure (ΔSBP), namely, Class 1 (i.e., the increasing class) consisted of 18 participants with low ΔSBP that increased continuously during the follow-up; Class 2 (i.e., the low-stable class) consisted of 610 participants with low ΔSBP that remained low throughout the follow-up; and Class 3 (i.e., the high-stable class) consisted of 32 participants with high ΔSBP at baseline that was relatively stable throughout the follow-up. Several parameters differed among subgroups, but only male sex [odds ratio (OR) = 4.687, 95% confidence interval (CI) = 1.024-21.459], lower supine diastolic blood pressure (DBP) (OR = 0.934, 95% CI = 0.876-0.996), and lower level of total protein at baseline (OR = 0.812, 95% CI = 0.700-0.941) were significant predictors of an increasing ΔSBP trajectory. Conclusion: This study provides new information on the longitudinal development of ΔSBP in patients with PD with distinct trajectories of rapidly increasing, low-stable, and high-stable class. The parameters such as male sex, lower supine DBP, and lower total proteins help to identify the rapidly increasing class.

Prognostic Factors for Cognitive Recovery Beyond Early Poststroke Cognitive Impairment (PSCI): A Prospective Cohort Study of Spontaneous Intracerebral Hemorrhage.

Background: Poststroke cognitive impairment (PSCI) has been increasingly recognized in patients, but some stroke survivors appear to show cognitive improvement beyond the acute stage. The risk factors associated with cognitive recovery after spontaneous intracerebral hemorrhage (ICH) onset have not yet been sufficiently investigated in prospective studies. Objective: We aimed to identify the trajectory of post-ICH cognitive impairment and the association of potential prognostic factors with follow-up cognitive recovery beyond early PSCI. Methods: In this stroke center-based cohort study, 141 consecutive dementia-free patients with spontaneous ICH were included and underwent Montreal Cognitive Assessment (MoCA) evaluation for cognitive function at baseline (within 2 weeks of ICH onset) and the shortened MoCA (short-MoCA) at a 6-month follow-up. To explore the prognostic factors associated with trajectory of cognition after an ICH onset, we adjusted for demographic and vascular risk factors, using multivariate logistic regression analysis. Results: Of the 141 ICH patients, approximately three quarters (106/141) were diagnosed with early PSCI (MoCA score <26) within 2 weeks of ICH onset. The multiple logistic regression indicated independent positive associations between risk of early PSCI and dominant-hemisphere hemorrhage [odd's ratio (OR): 8.845 (3.347-23.371); P < 0.001], mean corpuscular volume (MCV) [OR: 1.079 (1.002-1.162); P = 0.043], admission systolic blood pressure (sBP) [OR: 1.021 (1.005-1.038); P = 0.012]. Furthermore, 36% (33/90) of ICH survivors who had early PSCI exhibited cognitive recovery at the 6-month follow-up. After examining potential predictors through multiple linear regression based on stepwise, there were independent negative associations between cognitive recovery and dominant hemisphere hemorrhage [OR: 6.955 (1.604-30.162); P < 0.01], lobar ICH [OR: 8.363 (1.479-47.290); P = 0.016], years of education ≤ 9 [OR: 5.145 (1.254-21.105); P = 0.023], and MCV [OR: 1.660 (1.171-2.354); P = 0.004]. Baseline cognitive performance in the domains of visuospatial/executive function, attention, orientation, and language showed positive correlations with cognitive improvement (P < 0.05). Conclusion: In this cohort study of dementia-free survivors of ICH, our results show that one in three early PSCI survivors exhibit cognitive recovery, in relation to dominant-hemisphere hematoma, lobar ICH, educational history, and MCV levels. Future clinical trials including ICH survivors with cognitive dysfunction should assess these factors.